Relationship between use of acetaminophen,ibuprofen and intervertebral disc degeneration:a two-sample mendelian randomization study

LIU Yanxin; WANG Yantao; WEI Qipeng

doi:10.3969/j.issn.1674-666X.2025.03.001

Abstract：Objective To investigate the causal relationships between the use of acetaminophen,ibuprofen and intervertebral disc degeneration(IVDD).Methods GWAS datasets for acetaminophen and ibuprofen were obtained from the UK Biobank database,eligible single nucleotide polymorphisms(SNPs)were screened as instrumental variables,and SNPs related to three types of intervertebral disc degeneration from the FinnGen database were used as outcome variables for a two-sample Mendelian randomization(MR)analysis.The inverse variance weighted(IVW)method was employed as the primary approach to assess causal effects,supplemented by the MR-Egger and weighted median methods.Heterogeneity was evaluated using the Cochrane Q test,while horizontal pleiotropy was assessed using the MR-Egger and MR-PRESSO methods,and sensitivity was analyzed using the leave-one-out method.Results The IVW analysis revealed significant causal associations between acetaminophen use and cervical disc degeneration(OR=3.392,95%CI:1.609-7.147,P<0.001),lumbar disc degeneration(OR=2.678,95%CI:1.704-4.2010,P<0.001),and early lumbar disc herniation(OR=3.916,95%CI:1.918-7.996,P<0.001).No causal relationship was observed between ibuprofen usage and disc degeneration.Reverse MR analyses indicated that disc degeneration did not increase acetaminophen use;however,lumbar disc degeneration was positively associated with a higher likelihood of ibuprofen use(OR=1.006,95%CI:1.002-1.010,P<0.001).Conclusions The usage of acetaminophen showed a positive causal association with disc degeneration,suggesting that it may be a potential risk factor for disc degeneration.Conversely,lumbar disc degeneration was postively associated with increased ibuprofen use,implying that this condition may be a potential factor leading to greater ibuprofen consumption..